The present invention is directed to the use of hydroxyeicosatetraenoic acid compounds to treat ophthalmic inflammation. In particular, the invention relates to the use of such analogs in patients that are not suffering from dry eye for the treatment and prevention of ophthalmic inflammatory disorders involving cytokine secretion.
15-Hydroxyeicosatetraenoic acid (xe2x80x9c15-HETExe2x80x9d) is known to have inhibitory effects on leukotriene B4 production or its activity. See, for example, Zhu, et al., Skin Pharmacology and Applied Skin Physiology, 13(5):235-45 (September-October 2000); and Heitmann, et al., Experimental Dermatology, 4(2):74-8 (April 1995). 15-HETE is also reported to have minor anti-inflammatory properties in colitis. See Van Dijk, et al., Agents and Actions, 38 Spec. No. C120-1 (1993).
U.S. Pat. No. 5,696,166 (Yanni et al.) discloses compositions containing hydroxyeicosatetraenoic acid (xe2x80x9cHETExe2x80x9d) derivatives and methods of using them topically for treating dry eye. Yanni et al. discovered that compositions comprising HETE derivatives increase ocular mucin secretion and are thus useful in treating dry eye.
Other than the use of 15-HETE and certain analogs for treating dry eye, HETE compounds have not been reported to be useful in treating inflammatory conditions of the eye, particularly in treating conditions involving the production of pro-inflammatory cytokines. Reports of the effects of 15-HETE and analogs of 15-HETE on cytokine inhibition in other tissues are varied. See, for example, Denizot, et al., Cytokine, 11(8):606-10 (August 1999) (xe2x80x9c . . . 15-HETE (1 xcexcM to 0.1 nM) [has] no effect on the spontaneous and serum-induced production of IL-8 by human bone marrow stromal cellsxe2x80x9d); Denizot, et al., Cytokine, 10(10):781-5 (October 1998) (xe2x80x9c . . . 15-HETE . . . [has] no effect on the spontaneous, serum- and cytokine-induced IL-6 synthesis by bone marrow stromal cells; and WO 96/11908, which discloses that certain modified polyunsaturated fatty acids have the ability to suppress cytokine production and cytokine action and are useful as anti-malarial, anti-infective or anti-inflammatory agents. WO 96/11908 does not mention any ophthalmic inflammatory disorders.
The present invention is directed to methods of using HETE compounds to treat or prevent ophthalmic inflammatory conditions in patients that are not suffering from dry eye. In particular, the present invention is directed toward the topical ophthalmic use of HETE compounds to treat or prevent ophthalmic inflammatory conditions involving cytokines. Such ophthalmic inflammatory conditions include, but are not limited to, conjunctivitis; iritis; uveitis; episcleritis; scleritis; keratitis; endophthalmitis; and blepharitis.